The terminal complement components, C3-9, have the potential to participate in the host's defense against bacterial infection. In order to subserve this function, they must be activated and cleaved into fragments that are biologically active and can act as opsonins, chemotactic stimuli and anaphylatoxins. There are at least two mechanisms by which the terminal complement components may be activated; the classical pathway and the alternative pathway. Bacteria require the presence of specific antibody in order to activate the classical pathway, but little, if any, antibody is needed for bacteria to activate the alternative pathway. Thus, the classical pathway appears to be important in acquired immunity while the alternative pathway probably plays a role in natural immunity. The significance of the terminal complement components in the host's defense against bacterial infections has been demonstrated by 1) studies in animal models of complement deficiencies, 2) the experience in individual patients with complement deficiencies, and 3) the association of defective complement mediated serum activities with an increased susceptibility to infection in both newborn infants and in children with Sickle Cell Disease. We plan on investigating four interrelated aspects of the role of complement in the host's defense against bacterial infection: 1) What subcellular component of the pneumococcus activates that alternative pathway. 2) Is there an abnormality in the activation of the terminal complement components in newborn infants, and if so, what is the basis of it. 3) Does C3-9 play a role in the host's defense against bacterial meningitis and do they participate in the inflammatory process in the central nervous system. 4) What is the nature of the defect in the alternative pathway in children with Sickle Cell Disease.